CHAPTER 1 Principles of Cell and Membrane Function out vectorial transport of substances from one side of the epithelium to the opposite side. The ability to carry out vectorial transport is crucial for the functioning of several organ systems (e.g., the gastrointestinal tract and kidneys). In addition, some regions of the membrane contain lipids (e.g., sphingomyelin and cholesterol) that aggregate into what are called lipid rafts. These lipid rafts often have an association with specific proteins, which diffuse in the plane of the membrane as a discrete unit. Lipid rafts appear to serve a number of functions. One important function of these rafts is to segregate signaling molecules.
As much as 50% of the plasma membrane is composed of proteins. These membrane proteins are classified as integral, lipid-anchored, or peripheral.
Integral membrane proteins are imbedded in the lipid bilayer, where hydrophobic amino acid residues are associated with the hydrophobic fatty acyl chains of the membrane lipids. Many integral membrane proteins span the bilayer; such proteins are termed transmembrane proteins. Transmembrane proteins have both hydrophobic and hydrophilic regions. The hydrophobic region, often in the form of an α helix, spans the membrane. Hydrophilic amino acid residues are then exposed to the aqueous environment on either side of the membrane. Transmembrane proteins may pass through the membrane multiple times.
Thereisasuperfamilyofmembraneproteinsthatserveasreceptorsformanyhormones,neurotransmitters,andnumerousdrugs.ThesereceptorsarecoupledtoheterotrimericGproteinsandaretermedG protein–coupled receptors (see ).Theseproteinsspanthemembranewithsevenα-helicaldomains.Thebindingsiteofeachligandiseitherontheextracellularportionoftheprotein(largeligands)orinthemembrane-spanningportion(smallligands),whereasthecytoplasmicportionbindstotheGprotein.Thissuperfamilyofmembraneproteinsmakesupthethirdlargestfamilyofgenesinhumans.NearlyhalfofallnonantibioticprescriptiondrugsaretargetedtowardGprotein–coupledreceptors.
A protein can also be attached to the membrane via lipid anchors. The protein is covalently attached to a lipid molecule, which is then embedded in one leaflet of the bilayer. Glycosylphosphatidylinositol (GPI) anchors proteins to the outer leaflet of the membrane. Proteins can be attached to the inner leaflet via their amino-terminus by fatty acids (e.g., myristate or palmitate) or via their carboxyl-terminus by prenyl anchors (e.g., farnesyl or geranylgeranyl).
Peripheral proteins may be associated with the polar head groups of the membrane lipids, but they more commonly bind to integral or lipid-anchored proteins.
In many cells, some of the outer leaflet lipids, as well as many of the proteins exposed on the outer surface of the membrane, are glycosylated (i.e., have short chains of sugars, called oligosaccharides, attached to them). Collectively, these glycolipids and glycoproteins form what is called the glycocalyx. Depending on the cell these glycolipids and glycoproteins may be involved in cell recognition (e.g., cell surface antigens) and formation of cell-cell interactions (e.g., attachment of neutrophils to vascular endothelial cells).
Although plasma membrane proteins perform many important cellular functions, as noted previously, the remainder of this chapter focuses on one group of plasma membrane proteins: the membrane transport proteins, or transporters. It has been estimated that approximately 10% of human genes (≈2000) code for transporters. They are also targets for numerous drugs.